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| Item Type: | Article |
|---|---|
| Title: | Endothelial Epac1 facilitates YAP/TAZ controlled melanoma growth and angiogenesis |
| Creators: |
Wibowo, Yohanes Cakrapradipta, Ma, Nan, Ren, Yonggang, Cordero, Julio, Gahn, Johannes, Chen, Zihao, Levay, Magdalena, Ola, Roxana, Feng, Yuxi, Dobreva, Gergana  ORCID: https://orcid.org/0000-0002-4814-9416, Langer, Harald, Wieland, Thomas, Vettel, Christiane and Jansen, Sepp
|
| Abstract: | The RapGEF Epac1 has emerged as an important modulator of pro-angiogenic signalling pathways, including VEGF/VEGFR2. However, its specific role in tumor angiogenesis has remained unexplored. Here, we identify endothelial Epac1 as a critical driver of melanoma angiogenesis. Analysis of patient-derived melanomas revealed that Epac1 is markedly upregulated in tumor endothelial cells. Using both global and endothelial-specific Epac1 knockout mouse models, we demonstrate that Epac1 deletion reduced melanoma growth and vascularization following subcutaneous melanoma cell inoculation. Transcriptome profiling of tumor-associated endothelial cells from Epac1-deficient mice showed broad downregulation of pro-angiogenic and YAP/TAZ target genes. This was corroborated in vitro using an Epac1 knockout endothelial cell line, where VEGFR2 expression, YAP/TAZ nuclear translocation, and YAP/TAZ target gene transcription were all suppressed. Consistently, Epac1 deletion impaired VE-cadherin/VEGFR2 interaction, VEGF-dependent nuclear YAP/TAZ and transcriptional activity, and abolished endothelial cell alignment in response to shear stress. Collectively, our results reveal Epac1 as a central modulator of VEGFR2 and YAP/TAZ signalling, integrating angiogenic and mechanosensory cues during melanoma vascularization. |
| Keywords: | Epac1, Tumor Angiogenesis, Tumor Endothelial Cell, Melanoma, VEGFR2, YAP/TAZ, Mechanotransduction, Animals, Mice |
| Source: | Angiogenesis |
| ISSN: | 0969-6970 |
| Publisher: | Springer |
| Volume: | 29 |
| Number: | 4 |
| Page Range: | 72 |
| Date: | 23 September 2026 |
| Official Publication: | https://doi.org/10.1007/s10456-026-10080-6 |
| PubMed: | View item in PubMed |
| Related to: |
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